Pain and Laboratory Animals: Publication Practices for Better Data Reproducibility and Better Animal Welfare

Abstract

Scientists who perform major survival surgery on laboratory animals face a dual welfare and methodological challenge: how to choose surgical anesthetics and post-operative analgesics that will best control animal suffering, knowing that both pain and the drugs that manage pain can all affect research outcomes. Scientists who publish full descriptions of animal procedures allow critical and systematic reviews of data, demonstrate their adherence to animal welfare norms, and guide other scientists on how to conduct their own studies in the field. We investigated what information on animal pain management a reasonably diligent scientist might find in planning for a successful experiment. To explore how scientists in a range of fields describe their management of this ethical and methodological concern, we scored 400 scientific articles that included major animal survival surgeries as part of their experimental methods, for the completeness of information on anesthesia and analgesia. The 400 articles (250 accepted for publication pre-2011, and 150 in 2014–15, along with 174 articles they reference) included thoracotomies, craniotomies, gonadectomies, organ transplants, peripheral nerve injuries, spinal laminectomies and orthopedic procedures in dogs, primates, swine, mice, rats and other rodents. We scored articles for Publication Completeness (PC), which was any mention of use of anesthetics or analgesics; Analgesia Use (AU) which was any use of post-surgical analgesics, and Analgesia Completeness (a composite score comprising intra-operative analgesia, extended post-surgical analgesia, and use of multimodal analgesia). 338 of 400 articles were PC. 98 of these 338 were AU, with some mention of analgesia, while 240 of 338 mentioned anesthesia only but not post-surgical analgesia. Journals’ caliber, as measured by their 2013 Impact Factor, had no effect on PC or AU. We found no effect of whether a journal instructs authors to consult the ARRIVE publishing guidelines published in 2010 on PC or AC for the 150 mouse and rat articles in our 2014–15 dataset. None of the 302 articles that were silent about analgesic use included an explicit statement that analgesics were withheld, or a discussion of how pain management or untreated pain might affect results. We conclude that current scientific literature cannot be trusted to present full detail on use of animal anesthetics and analgesics. We report that publication guidelines focus more on other potential sources of bias in experimental results, under-appreciate the potential for pain and pain drugs to skew data, and thus mostly treat pain management as solely an animal welfare concern, in the jurisdiction of animal care and use committees. At the same time, animal welfare regulations do not include guidance on publishing animal data, even though publication is an integral part of the cycle of research and can affect the welfare of animals in studies building on published work, leaving it to journals and authors to voluntarily decide what details of animal use to publish. W...

Side effects of pain and analgesia in animal experimentation

“…Despite the standard use of multimodal therapies in humans and large laboratory species, their use remains uncommon in small rodents 2 . Multimodal analgesia is a concept that involves different classes of analgesics and/or different sites of drug administration.…”

“…A recent review on reporting practices for anesthesia and analgesia protocols after invasive animal procedures revealed that many published studies do not include pain relief and do not report, or do not completely report, the anesthetic and analgesic measures involved 2 . The pain management protocol chosen, as well as any untreated pain, has the potential to affect scientific results and increase the variability of data, thereby hampering the reproducibility of experiments substantially.…”

The antinociceptive effect of resveratrol in bone cancer pain is inhibited by the Silent Information Regulator 1 inhibitor selisistat

“…All behavioural tests were performed between 9:00 and 13:00 h, and mice were allowed to habituate to the housing facility for 1 h before the beginning of experiments. The experimental procedures were approved by the Bioethics Committee of the Faculty of Medicine, University of Chile, (protocol CBA0721 from January 2015) and were in agreement with recently published animal welfare norms on pain management and with the Guide for the Care and Use of Laboratory Animals of NIH . To determine the number of required mice in each experimental group, a sample size power analysis was conducted by using the G*Power 3 Software (Heinrich Heine Universität Düsseldorf, Düsseldorf, Germany) .…”

Expanding the 3R principles

“…A recent study assessed publications that involve major surgery on laboratory animals whether these completely describe the procedures and adherence to animal welfare norms, found that whether the journal asked authors to adhere to ARRIVE publishing guidelines or not had no effect on the quality of the methods section [8]. A recent study assessed publications that involve major surgery on laboratory animals whether these completely describe the procedures and adherence to animal welfare norms, found that whether the journal asked authors to adhere to ARRIVE publishing guidelines or not had no effect on the quality of the methods section [8].…”